Program Director/Principal Investigator (Last, First, Middle): Project Summary/Abstract This project will explore calcium-release-activated calcium channels (CRAC) as a potential therapeutic target in a laboratory stroke model. Stroke is a significant health problem in developed nations, but definitive treatments are few, and no treatments are available which can rescue brain cells dying from ischemia. Microglia are the brain's resident immune cell, and many studies have now shown that when activated, they contribute negatively to stroke outcome. Thus, strategies to inhibit microglial functions could prove therapeutic. Recent work by other labs has focused on the role of CRAC channels in inflammatory cells such as T cells, mast cells and neutrophils, and other inflammatory conditions such as autoimmune disease and acute pancreatitis; however, very little work has been published on CRAC channels as they pertain to microglia or inflammation in the ischemic brain. Preliminary work in our lab showed that these inhibitors block microglial activation and protect the brain from experimental traumatic brain injury. This project will study novel inhibitors of CRAC channels in an in vivo model of stroke. Mice exposed to middle cerebral artery occlusion will be treated with novel CRAC channel inhibitors to see if this will improve neurological outcomes, and if this is due to an anticipated anti-inflammatory effect. This project will explore whether this compound will improve outcome in experimental stroke in both male and female animals. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page